Alvespimycin

Alvespimycin (17-DMAG) is a potent inhibitor of Hsp90, binding to Hsp90 with an EC₅₀ of 62 nM. IC50 & Target:EC50: 62 nM (Hsp90)^[1] In Vitro:Alvespimycin (17-DMAG) inhibits the growth of the human cancer cell lines SKBR3 and SKOV3, which overexpress Hsp90 client protein Her2, and causes down-regulation of Her2 as well as induction of Hsp70 consistent with Hsp90 inhibition, for Her2 degradation with EC₅₀ of 8 nM and 46 nM in SKBR3 and SKOV3 cells, respectively; for Hsp70 induction with EC₅₀ of 4 nM and 14 nM in SKBR3 and SKOV3 cells, respectively^[1].
Compared with the vehicle control, Alvespimycin (17-DMAG) dose-dependent apoptosis (P<0.001 averaged across 24- and 48-hour time points) at concentrations of 50 nM to 500 nM, which represent pharmacologically attainable doses. Similar to many other agents, Alvespimycin (17-DMAG) also demonstrates time-dependent apoptosis (P <0.001, averaged across all doses) in chronic lymphocytic leukemia (CLL) cells with extended exposure from 24 to 48 hours. In addition,Alvespimycin (17-DMAG) is much more potent after 24 and 48 hours of treatment than 17-AAG^[2]. In Vivo:The tumors are grown for two months before the start of i.p. injections every four days over one month with 0, 50, 100 and 200 mg/kg dipalmitoyl-radicicol or 0, 5, 10 and 20 mg/kg Alvespimycin (17-DMAG). Despite sample heterogeneity, the HSP90 inhibitor-treated animals have significantly lower tumour volumes than the vehicle control-treated animals^[3].